Debiopharm’s Pre-Clinical Proof-Of-Concept Research Unveils the Potential of Novel MultiLINK Linker Technology to Overcome Tumor Resistance

Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standards of care to cure cancer and infectious diseases, today announced their latest research on antibody drug conjugate (ADC) research released at World ADC San Diego 2026. Results highlighted the pre-clinical performance of a selection of linker technology from Debiopharm’s MultiLINK™ Linker Technology suite (MLINK Select, MLINK Duo and MLINK HiSol), revealing positive implications for the development of next generation ADCs and for the future of cancer patients that require more innovative therapies to overcome their disease.

Despite remarkable progress in the ADC field, many cancers remain difficult to treat due to biological complexities that challenge current-generation therapies. Tumor heterogeneity can enable cancer cells with low or absent target expression to escape treatment, while acquired resistance to single-payload ADCs may emerge over time and compromise durable responses. Furthermore, premature linker cleavage can lead to systemic payload release and off-target toxicities, restricting the therapeutic index of ADCs. These limitations underscore the urgent need for next-generation ADC technologies, including innovative linker-payload systems and dual-payload linker approaches, designed to address resistance, broaden anti-tumor activity while remaining tolerable, and ultimately improve outcomes for patients facing cancer.

MLINK Select MMAE: Novel Linker-Payload Research

Research results presented at World ADC demonstrated that novel linker MLINK Select releases controlled intracellular MMAE and substantially widens the therapeutic index of vedotin-based MMAE ADCs in preclinical models, while maintaining high-level anti-tumor activity. Notably, efficacy was demonstrated in specific models resistant to approved ADC therapies. Data presented reveal that MLINK Select MMAE achieves: more selective intracellular cleavage, stepwise/controlled MMAE release, higher plasma stability, minimal circulation of free MMAE, improved therapeutic index, and maintenance of anti-tumor activity.

“We recognize the remarkable progress made by ADCs, but many patients, however, continue to face disease progression due to treatment resistance, tumor heterogeneity, and dose-limiting toxicities. We believe that next generation ADC innovation can make a difference by focusing not only on what is delivered to cancer cells, but also on how it is delivered, particularly regarding linker selection,” explained Noemie Luong, Associate Principal Scientist, Debiopharm.“Our preclinical findings demonstrate that precise control of payload release through innovative linker engineering has the potential to expand the therapeutic window while maintaining anti-tumor activity.“

MLINK DUO: Synergystic activity with Dual-Payload linker

Strong proof-of-concept data was released for Debiopharm's next-generation dual-payload ADC, MLINK Duo, a linker technology that allows conjugation of two payloads to the same antibody. Results revealed that our dual-payload ADCs produced synergistic antitumor activity, including in models with low sensitivity to individual payloads, demonstrating the potential to synergistically overcome resistance and tumor heterogeneity. Enhanced efficacy was achieved while preserving critical ADC properties, including plasma stability, antibody pharmacokinetics and a favorable preclinical safety profile.

“With MLINK Duo, we observed the potential to exploit payload synergy while reducing resistance mechanisms,”expressed Viktoriia Postupalenko, Senior Scientist/ Project Manager, Drug Research and Development, Debiopharm. “As dual-payload conjugation did not compromise antibody pharmacokinetics, we confirmed that increased payload complexity can be achieved without sacrificing desired ADC properties. By advancing smart dual-payload designs such as with MLINK Duo, we aim to help unlock more effective and better tolerated treatment options for patients fighting cancer.”

MLINK HiSol: Unlocking new ADC therapeutic strategies

Further research showcased modular cathepsin B-cleavable MLINK HiSol linkersdesigned to overcome common ADC development challenges, including payload solubility, stability, aggregation, and efficient intracellular release. The versatility of this linker type was particularly highlighted showing that it is not limited to conventional ADC payloads such as MMAE and exatecan, but can potentially unlock new ADC therapeutic strategies based on targeted pathway inhibition with precision oncology payloads such as ATR inhibitors, CHK1 inhibitors, and NAMPT inhibitors.

“Targeted small-molecule inhibitors are traditionally difficult to use as ADC payloads,”Noemie Luong added,“We’re excited that the results with MLINK HiSol are opening the door towards more payload possibilities to help patients fight cancer. Now that we’ve seen early evidence that MLINK HiSol can enable delivery of targeted small-molecule inhibitors, we can explore ADCs beyond conventional cytotoxic mechanisms.”

Debiopharm’s ADC Expertise

We’re developing fit-for-purpose antibody-drug conjugates through a tailored “Trifecta” approach combining: strategic target selection, innovative MultiLink™ linker technology, and smart payload choices. Our ADC portfolio includes first-in-class and best-in-class candidates: Debio1562M, a CD37-targeted ADC for the treatment of acute myeloid leukemia and myelodysplastic syndromes, and Debio2512, an HER3-HER2-targeted ADC for solid tumors, as well as other ADCs (undisclosed targets) including Debio0633 and Debio2511. We are actively partnering to access innovative targets, co-develop, or out-license our ADC programs. We are also seeking to collaborate with developers interested in exploring our MultiLINK^TM Linker Technology Suite to solve complex linker challenges, helping to enable both high drug-to-antibody ratios (DAR) and high stability.

We have strong in-house capabilities and in-depth expertise spanning ADC conjugation and optimization, pharmacokinetics/pharmacodynamics, toxicology, translational medicine, pharmaceutical, clinical development, and supply chain management. We continue to invest in and explore potential game-changing technologies, such as novel and dual payloads.​

Debiopharm's Commitment to Patients

Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then hand stewardship to large pharmaceutical commercialization partners to maximize patient access globally.

For more information, please visit www.debiopharm.com
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